DESCRIPTION: (Applicant's Abstract) Among the health and medical consequences of long-term marijuana use, the possibility of residual neuropsychological effects - such as impairments of attention, memory and other cognitive functions - remains an area of concern. But these effects are still poorly understood because of the methodological limitations of existing studies. Specifically, many studies have examined marijuana users with only modest total lifetime exposure to the drug, and, thus, are at risk for a type II error - failing to detect an effect if one in fact exists. Of the remaining studies which have examined users with substantial exposure, most tested users after only 24-48 hours of abstinence from marijuana and in many cases the abstinence period was not supervised. Thus, any deficits observed may have simply reflected a residue of recently smoked cannabinoids in the brain, or alternatively, acute withdrawal effects from abrupt discontinuation of marijuana. Therefore, further study is clearly required to resolve the question of whether long-term marijuana use produces clinically meaningful residual neurotoxicity. The study proposed in this application seeks to address the methodological problems of earlier investigations in several ways. First, the investigators will study individuals who have smoked marijuana at least 5000 times (the equivalent of smoking once per day for 13.7 years) in order to minimize the risk of a type II error as described above. Second, users will receive serial neuropsychological tests over the course of a 28-day period of abstinence from marijuana and other drugs, monitored by daily observed urine collections. This technique will allow the investigators to distinguish between temporary impairment due either to a residue of drug or to withdrawal effects, and prolonged impairment due to frank neurotoxicity. A feasibility study, performed by the investigators, has demonstrated that it is possible to recruit substantial numbers of long-term heavy marijuana users (mean lifetime number of episodes of smoking = 19,000), age 30 to 54, of both genders and a range of ethnic and socioeconomic groups, who would be willing to participate in a study of this proposed design. A battery of neuropsychological tests, many of which have already been used by the investigators in a previous study of marijuana effects in college students, has been chosen to assess a wide range of cortical functions, including particularly the attentional/executive functions found impaired in previous studies of marijuana users at this center and others. Additional neuropsychological tests of the investigators' own design and additional analyses of serial urine and blood samples at the Addiction Research Center in Baltimore, MD, will provide further data on the relationship between marijuana use, cannabinoid levels and various types of possible neuropsychological effects. Given the widespread use of marijuana among contemporary Americans, these results should provide important information for legislative and regulatory bodies concerned with this drug.